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hormonal and metabolic factors, including blood glucose levels, exercise, sex hormones, glucocorticoids and thyroid hormone. At the cellular level, the pleiotropic action of GH is elicited by its interaction with the GH receptor (GHR). GHR belongs to class I cytokine receptor superfamily that includes receptors for PRL, leptin and interleukins. The predicted molecular mass of GHR is ~70 kDa. An initiating event in this interaction is the activation of janus kinase 2 (JAK2), a GHR-associated tyrosine kinase. According to the original model, a single molecule of GH sequentially binds to two GHRs to induce dimer formation, which then increases the affinity of each GHR for JAK2. However, this original concept was revised recently by a study, which indicates GHRs either exist as a dimer 2 or as a heterodimer with the prolactin receptor 3 and that GH binding brings about a conformational change in the dimer that is important for the postreceptor signalling cascade, including activation of JAK2. Activated JAK2 phosphorylates itself and also the tyrosine residues in the cytoplasmic domain of GHR. These phosphotyrosines are thought to form high-affinity binding sites that recruit a variety of signalling proteins containing phosphotyrosine-binding domains, including signal transducers and activators of transcription (STAT) family proteins. The activated GHR-JAK2 complex can phosphorylate at least four members of the STAT family (STATs 1, 3, 5A and 5B), leading to their dimerisation, nuclear translocation and activation of transcription. Another pathway important in GH-regulated gene transcription is the mitogen-activated

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